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PDGFRA Mutation Analysis Test

Last updated May 27, 2017

The PDGFRA Mutation Analysis Test is a genetic test that detects abnormalities in the PDGFRA gene. It is used to diagnose cancer.


What are other Names for this Test? (Equivalent Terms)

  • CD140 Antigen-Like Family Member A Mutation Analysis Test
  • GAS9 Mutation Analysis Test
  • Platelet-Derived Growth Factor Receptor Alpha Mutation Analysis Test

What is PDGFRA Mutation Analysis Test? (Background Information)

  • PDGFRA mutation refers to an alteration in the PDGFRA gene. It is associated with cancers of the gastrointestinal, immune, and other systems
  • The PDGFRA gene gives instructions for the PDGFRA protein (platelet derived growth factor receptor alpha protein). The PDGFRA protein is a type of receptor tyrosine kinase (RTK)
  • RTKs reside on the surfaces of certain cells, where they act as antennas that receive signals from outside the cell and transmit them inside the cell
  • The PDGFRA protein is found on the membranes of cells of the gastrointestinal and immune systems, among others. As its name implies, the signal that the PDGFRA protein recognizes and binds is a chemical called platelet derived growth factor
  • Once bound with platelet derived growth factor, PDGFRA launches a chain of events inside the cell that leads to the growth and division of the cell. PDGFRA is necessary for the survival and movement of cells, and for maintaining the balance of cell populations
  • Alterations in the PDGFRA gene may result in a defective PDGFRA protein that may activate itself independently of platelet derived growth factor. The defective PDGFRA is overactive as a result of it no longer needing platelet derived growth factor to bind in order to activate
  • Alterations in the PDGFRA gene that affect PDGFRA protein function may interfere with normal growth and division of cells, causing cancer
  • The PDGFRA Mutation Analysis Test is a genetic test that detects abnormalities in the PDGFRA gene. It is used to diagnose cancer. It also aids in the treatment of cancers by guiding selection of therapeutic drugs, including disqualifying certain drugs from use

The molecular testing, in general, can be performed using a variety of methods. Some of these methods include:

  • In situ hybridization technique, such as fluorescence in situ hybridization (FISH)
  • Immunohistochemistry (IHC)
  • Next-generation sequencing (NGS)
  • Polymerase chain reaction (PCR)
  • Comparative genomic hybridization (CGH)
  • Karyotyping including spectral karyotyping
  • mRNA analysis
  • Tissue microarrays (TMAs)
  • Southern blot test
  • Northern blot test
  • Western blot test
  • Eastern blot test

The methodology used for the test may vary from one laboratory to another. 

Note: Molecular testing has limitations due to the molecular method and genetic mutational abnormalities being tested. This can affect the results on a case-by-case basis. Consultation with your healthcare provider will help in determining the right test and right molecular method, based on individual circumstances.

What are the Clinical Indications for performing the PDGFRA Mutation Analysis Test?

Following are the clinical indications for performing the PDGFRA Mutation Analysis Test: 

  • Abdominal (belly) discomfort or pain
  • A mass or swelling in the abdomen
  • Nausea, vomiting
  • Feeling full after eating only a small amount of food
  • Loss of appetite
  • Weight loss
  • Problems swallowing (for tumors in the esophagus)

In general, the molecular genetic testing is undertaken in the following situations: 

  • To assist (and in some cases, confirm) the initial diagnosis
  • To distinguish other tumors/conditions that have similar histological features, when examined by a pathologist under the microscope
  • To help in determining treatment options
  • To confirm recurrence of the tumor: Tumor recurrence can either be at the original tumor site, or at a distant location (away from the initial site)

How is the Specimen Collected for PDGFRA Mutation Analysis Test?

Following is the specimen collection process for PDGFRA Mutation Analysis Test:

The specimen sample requirements may vary from lab to lab. Hence, it is important to contact the testing lab for exact specimen requirements, before initiating the testing process.

  • Sample on which the test is performed may include:
    • Fresh tumor tissue during biopsy
    • Formalin-fixed paraffin-embedded solid tumor tissue (FFPE tumor tissue), often referred to as paraffin block of the tumor
    • Unstained tissue slides
  • Process of obtaining the sample: As outlined by the laboratory testing facility
  • Preparation required: As outlined by the laboratory testing facility

Note:

  • In some cases, a different source of specimen (such as peripheral blood, bone marrow biopsy specimen, or other body fluids) may be acceptable to the laboratory performing the test
  • Occasionally, additional samples may be required to either repeat the test or to perform follow-up testing
  • Depending on the location of testing, it may take up to 2 weeks’ turnaround time, to obtain the test results
  • Many hospitals preserve the paraffin blocks for at least 7 years. In general, older paraffin blocks (over 5 years) may affect the detection of specific mutations, due to degradation of the tumor specimen over time

Cost of PDGFRA Mutation Analysis Test:

  • The cost of the test procedure depends on a variety of factors, such as the type of your health insurance, annual deductibles, co-pay requirements, out-of-network and in-network of your healthcare providers and healthcare facilities
  • In many cases, an estimate may be provided before the test is conducted. The final amount may depend upon the findings during the test procedure and post-operative care that is necessary (if any)

What is the Significance of the PDGFRA Mutation Analysis Test Result?

A mutation in the PDGFRA gene indicates a positive result for the PDGFRA Mutation Analysis Test. This may point to a diagnosis of any of the following:

  • Gastrointestinal stromal tumor (GIST)
  • PDGFRA-associated chronic eosinophilic leukemia
  • Inflammatory fibroid polyps

The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario.

Additional and Relevant Useful Information:

  • PDGFRA mutation most notably occurs in a location of the chromosome called 4q12 i.e., the long arm (q) of chromosome 4 in position 12
  • Many laboratories may not have the capability to perform this test. Only highly-specialized labs with advanced facilities and testing procedures may perform this test

Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider, the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.

What are some Useful Resources for Additional Information?

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/gastrointestinal-stromal-tumor-gist/

Please visit our Laboratory Procedures Center for more physician-approved health information:

http://www.dovemed.com/common-procedures/procedures-laboratory/

References and Information Sources used for the Article:

https://ghr.nlm.nih.gov/primer/testing/genetictesting (accessed on 05/10/2017)

https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5806a1.htm (accessed on 05/10/2017)

http://www.nature.com/gim/journal/v10/n5/full/gim200852a.html (accessed on 05/10/2017)

http://pediatrics.aappublications.org/content/106/6/1494 (accessed on 05/10/2017)

PDGFRA gene - Genetics Home Reference. (n.d.). Retrieved from https://ghr.nlm.nih.gov/gene/PDGFRA#location

Signs and Symptoms of Gastrointestinal Stromal Tumors. (n.d.). Retrieved from http://www.cancer.org/cancer/gastrointestinal-stromal-tumor/detection-diagnosis-staging/signs-symptoms.html

Helpful Peer-Reviewed Medical Articles:

Carrano, A. V., et al. Measurement and purification of human chromosomes by flow cytometry and sorting. Proceedings of the National Academy of Sciences 76, 1382–1384 (1979)

Drets, M. E., & Shaw, M. W. Specific banding patterns of human chromosomes. Proceedings of the National Academy of Sciences 68, 2073–2077 (1971)

Druker, B. J. Perspectives on the development of a molecularly targeted agent. Cancer Cell 1, 31–36 (2002)

Parra, I., & Windle, B. High resolution visual mapping of stretched DNA by fluorescent hybridization. Nature Genetics 5, 17–21 (1993) doi:10.1038/ng0993-17

Pinkel, D., et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nature Genetics 20, 207–211 (1998) doi:10.1038/2524

Speicher, M. R., et al. Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nature Genetics 12, 368–375 (1996) doi:10.1038/ng0496-368

Verhaak, R. G., Hoadley, K. A., Purdom, E., Wang, V., Qi, Y., Wilkerson, M. D., ... & Alexe, G. (2010). Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer cell, 17(1), 98-110.

Janeway, K. A., Kim, S. Y., Lodish, M., Nosé, V., Rustin, P., Gaal, J., ... & Lai, A. H. (2011). Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proceedings of the National Academy of Sciences, 108(1), 314-318.

Merkelbach-Bruse, S., Dietmaier, W., Füzesi, L., Gaumann, A., Haller, F., Kitz, J., ... & Schneider-Stock, R. (2010). Pitfalls in mutational testing and reporting of common KIT and PDGFRA mutations in gastrointestinal stromal tumors. BMC medical genetics, 11(1), 106.

Heinrich, M. C., Griffith, D., McKinley, A., Patterson, J., Presnell, A., Ramachandran, A., & Debiec-Rychter, M. (2012). Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clinical cancer research, 18(16), 4375-4384.

Wozniak, A., Rutkowski, P., Piskorz, A., Ciwoniuk, M., Osuch, C., Bylina, E., ... & Kruszewski, W. (2012). Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumours (GIST): Polish Clinical GIST Registry experience. Annals of oncology, 23(2), 353-360.

Pantaleo, M. A., Astolfi, A., Indio, V., Moore, R., Thiessen, N., Heinrich, M. C., ... & Martelli, P. L. (2011). SDHA Loss-of-Function Mutations in KIT–PDGFRA Wild-Type Gastrointestinal Stromal Tumors Identified by Massively Parallel Sequencing. Journal of the National Cancer Institute.

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 27, 2017
Last updated: May 27, 2017